The Promise of PrEP for HIV Prevention

A large international study among gay men and transgender women,the so-called iPrEx trial, suggested that pre-exposure prophylaxys (PrEP) by a tenofovir/emtricitabine combination can reduce the risk of HIV infection by at least 92% when the pills are taken consistently. Other trials subsequently confirmed PrEP effectiveness. 

PrEP is not intended as a stand-alone intervention, but rather as part of a multi-faceted strategy involving the use of condoms as well as regular follow-ups including for HIV and other sexually transmitted diseases testing

By Marieke Bak

Research Intern at AFEW International

The Promise of PrEP for HIV Prevention

 

Despite significant progress in the past decades, the global HIV/AIDS epidemic remains a major public health issue. In 2015, an estimated 36.7 million people worldwide were living with HIV, representing a global prevalence of 0.8%. Declines in new HIV infections have slowed in recent years, and in some regions the incidence of HIV continues to grow. One of the most rapidly accelerating epidemics is currently taking place in Eastern Europe and Central Asia, where new HIV infections rose by 57% between 2010 and 2015. Thus, the fight against HIV continues, and has become intensified since the United Nations committed to ending the epidemic by the year 2030.

Recognising that universal access to testing and treatment alone will not stop the epidemic, UNAIDS has been calling for a “much stronger primary prevention response” and recommends that 25% of national HIV budgets is spent on prevention. Moreover, countries are urged to use a combination approach to HIV prevention, consisting of behavioural, biomedical and structural interventions.

However, current biomedical and behavioural interventions are of limited effectiveness in many settings. Behavioural strategies such as celibacy and mutual monogamy are not reliable or realistic for many people worldwide. In addition, negotiating condom use can be difficult or impossible in some settings, or the effect of condoms on sexual pleasure may lead to non-use. Moreover, it was found that self-reported consistent condom use only reduces the risk of HIV acquisition by 63% to 72% among men who have sex with men (MSM), one of the key populations at risk for HIV infection, and by 80% among heterosexual men and women. Treatment as prevention (TasP) also has limitations, since it is dependent upon partners’ medication adherence to ensure suppressed viral load. Moreover, viral suppression rates are not high enough to prevent new infections solely through TasP.

Considering these limitations, there has been a need for additional prevention strategies that are effective and do not place the risk of HIV infection in other people’s hands. Provision of pre-exposure prophylaxis (PrEP) may be such a strategy. PrEP is a daily pill consisting of a combination of tenofovir/emtricitabine, two anti-retroviral drugs. It is branded by Gilead Sciences as Truvada which was approved for prevention in 2012 by the Food and Drug Administration (FDA) in the United States. In contrast to PEP, or post-exposure prophylaxis, PrEP is taken before exposure to HIV to prevent any possible transmission. It works by blocking an enzyme called HIV reverse transcriptase, thereby preventing HIV from establishing itself in the body.

A large international study among gay men and transgender women, the so-called iPrEx trial, suggested that PrEP can reduce the risk of HIV infection by at least 92% when the pills are taken consistently. Other trials subsequently confirmed PrEP effectiveness.  However, because it is not 100% effective and because it does not protect from other sexually transmitted diseases (STDs), PrEP is not intended as a stand-alone intervention, but rather as part of a multi-faceted strategy involving the use of condoms as well as regular follow-ups. These visits should take place every three months and consist of HIV testing, testing for other STDs, assessment of side effects, and counselling on medication adherence and risk reduction.

In addition to the promising effectiveness data, one of the main advantages of PrEP is that it puts HIV prevention directly under the control of the at-risk individual. Because PrEP separates the act of prevention from the sexual encounter, it can be used without sexual partners knowing. This makes PrEP a “gender-sensitive” strategy: it does not require consent from a male partner, which is a major advantage in settings where women are disempowered to discuss condom use.

With PrEP, the individuals become empowered to take control of their own health, and it has been suggested that PreP might “transform HIV infection just like hormonal contraception transformed family planning”. Also, it enables those who are in serodiscordant relationships to have sex without condom, and is a welcome new option for couples who wish to conceive. Lastly, a well-functioning PrEP programme with regular follow-ups might have the added benefit of strengthening healthcare systems and HIV services.

There are some side effects associated with Truvada for PrEP, although these are generally minor symptoms such as nausea and headaches that resolve within a few weeks. In rare cases, people may experience small changes in kidney function or a decrease in bone mineral density. An updated version of Truvada known as Descovy, that is thought to have fewer side effects, is currently being investigated in the so-called “Discover study”.

Because PrEP does not prevent transmission of other sexually transmitted diseases, there have been fears that PrEP might be used as a “party drug” and lead to increasing rates of other STDs. In fact, in the iPrEx study as well as in a meta-analysis by the World Health Organisation (WHO), it was shown that PrEP does not lead to an increase in the number of STDs and has no effect on condom use. On the contrary, a recent study found that PrEP use can actually reduce the incidence of STDs among men who have sex with men, because it involves routine screening and treatment of other STDs.

The World Health Organization now recommends that PrEP should be offered as a choice to key populations affected by HIV as well as to anyone else at substantial risk of HIV infection. However, Truvada is currently approved for use as PrEP only in a handful of countries, while a number of countries are conducting pilots, and access is expanding slowly across the world. Global availability remains limited at 2% of the target set by UNAIDS to get three million people on PrEP by 2020.

At the moment, Truvada for PrEP has been approved in the United States, Canada, Australia, Peru, South Africa, Kenya, Zimbabwe, Israel, and the European Union. Approval is pending in Brazil and Thailand. In the European Union, PrEP has been approved by the European Medicines Agency (EMA) although the implementation of PrEP programmes is the responsibility of each member state separately. To date, only France and Norway have made PrEP available as part of their healthcare system. Scotland recently announced that it will do the same.

The hesitation to fund PrEP often stems not only from seemingly unfounded worries for risk compensation, but also from the high cost of PrEP. Even in low- and middle income countries where generic versions of Truvada are generally available, drug prices still present a barrier to the accessibility of PrEP and may lead to developing countries having to make trade-offs between prevention and treatment. Indeed, PrEP is more expensive than other HIV prevention methods, but it can be a cost-effective tool in some settings, especially when delivered to key population. According to the WHO, offering PrEP can be cost-effective when the HIV incidence is greater than 3 per 100 persons. A study published in the Lancet reported that by preventing the costs of lifetime HIV treatment, PrEP may eventually lead to healthcare savings, especially when the drug patents expire and the cost drops.

Since it is widely recognised that treatment alone is not sufficient to eradicate HIV, and given the high effectiveness of PrEP, countries should make an effort to provide access to PrEP among those at risk of HIV infection. While keeping in mind that PrEP is part of a combination prevention approach, scaling up of PrEP programmes will be a significant step towards ending the global HIV/AIDS epidemic.

The dilemma in Controlling the Contact between Humans and Live Poultry: Lessons from a Re-emerging Human H7N9 Influenza Case in Shanghai China

Since the first H7N9 influenza case was diagnosed in 2013, the disease has involved more than ten provinces and municipalities of China. There are a number of cases diagnosed in the years 2014 and 2015, most of whom had a history of live poultry contact, although there are already strict limitations on the purchase of live poultry. This reflects the dilemma between the needs of disease prevention and pre-existing social economic factors. Here we discuss this issue starting from a recent case of human H7N9 influenza diagnosed in Shanghai

The dilemma in Controlling the Contact between Humans and Live Poultry

Lessons from a Re-emerging Human H7N9 Influenza Case in Shanghai China

  Hongzhou-Lu

By Hongzhou Lu*

and Tangkai Qi, Jiaying Shen

Division of Infectious Disease

Shanghai Public Health Clinical Centre affiliated to Fudan University

 

The Case

A 52 years old man in Shanghai bought live chicken and slaughtered it at home on March 23rd , 2015. 3 days later he started to have a fever of 38.6 oC accompanied with chills. He had neither respiratory symptom, gastrointestinal symptom nor other discomforts. He took antipyretic drug by himself and fever relieved. On March 27th the body temperature went as high as 39 oC. Chest X-ray at a local hospital showed “Increased veins of bilateral lung”. The doctor considered “viral upper respiratory infection” and prescribed non-steroidal anti-inflammatory drug. On April 1st the patient had a fever as high as 39.6 oC accompanied with nonproductive cough. So he went to the District Central Hospital. Chest CT scan showed “inflammation on the lower lobes of both lungs”. A rapid swab antigen test showed a positive result of influenza A. He was given a combined therapy of oseltamivir phosphate at 150mg twice daily), levofloxacin 400mg per day, imipenem cilastatin 2g per day, methylprednisolone 40mg per day, human immunoglobulin 20g per day, as well as symptomatic treatment. The patient’s condition deteriorated and developed breath shortness on April 5th. A repeated chest CT also showed more severe lung foci. Throat swab was collected and sent to local CDC on April 5th. On April 6th, there was a positive H7N9 PCR report. The patient was confirmed with a diagnosis of human H7N9 avian influenza and transferred to our hospital. He was continued with oseltamivir 150mg twice daily treatment for 7 days and discharged on April 15th.

Discussion

There is an established link between human H7N9 influenza and contact with live poultry markets [1,2]. Soon after the outbreak of human H7N9 influenza, the Shanghai municipal government totally suspended live poultry trade according to the advices from experts [3,4]. Other cities also took similar measures wherever human cases were reported. Surveys estimated that closure of live poultry markets (LPMs) reduced the daily number of human infections by 97-99%, respectively [5,6]. These policies were extended in the epidemic seasons of the years 2014 and 2015. In non-epidemic seasons, live poultry trade was permitted only in isolated regions of designated markets, with close monitoring on the birds and environment.

The Shanghai municipal fully suspended live poultry purchase from February 19th to April 30th, 2015. However this patient developed flu like symptoms three days after contact with live poultry on March 23rd. Then we learned that he bought it from Taicang city near Shanghai, where live poultry trade has also been suspended. It turned out that the patient traded with an unlicensed individual trader nearby a market at Taicang. This reflects a long lasting dilemma between the needs of infectious diseases prevention and social economic needs.

Certain factors might have contributed to this dilemma:

  • Dietary needs and cultural habits: chefs and home cooks have become accustomed to buying live birds, slaughter it and prepare dishes which fit people’s tastes. This demand is even more robust during traditional festivals.
  • Economic benefits: Human H7N9 avian influenza outbreaks lead to a direct economic loss of over 6.5 billion US dollars within 3 months, estimated by the Chinese Ministry of Agriculture. Accompanied is the shutdown or bankruptcy of enterprises that keep or purchase live poultry. Even though live poultry markets are shut down, dietary and livelihood needs drive people to purchase live poultry beyond the monitoring.
  • Part of the H7N9 influenza patients had a history of keeping domestic poultry instead of contacting with live poultry market. Despite of the progress of urbanization, there are a large number of people staying in rural areas, maintaining self-sufficient rural economy including backyard poultry. Household of poultry is deeply rooted in the local farming culture and daily life, posing additional challenge to restrict the contact between human and poultry.

At the same time, a number of different subtypes of avian influenza viruses is emerging in live poultry markets, some of which have resulted in human disease (Table 1). It is necessary and urgent to control the spread of avian influenza virus from birds to humans in a vast and populated country like China, so that to better protect the health of the people and prevent endemic or pandemic influenza. To better manage the production and trading of live poultry, several measures might be considered including:

  • Periodic public hearing involving animal scientist, infectious disease specialists, epidemiologists, poultry enterprises, customers and policy makers. So that they can develop strategies taking into account both the needs of public health and concerns of private stakeholders.
  • More public advertisement about the knowledge of infectious disease prevention and control, especially that about H7N9 influenza. Given H7N9 avian influenza predominantly occurs in middle-aged and old people, special efforts should be made to educating this population.
  • Fast development of avian H7N9 influenza vaccine (to be provided for free or low-cost to poultry farms and housekeepers).
  • Economic compensation to encourage family farmers stop poultry keeping, together with employment support to live poultry salesmen after closing LPMs.
  • Legislation and law enforcement in guaranteeing the security of public health. Joint power of law and human emotion will guide the public to establish a healthy and safe lifestyle.

Table 1 Avian influenza in human and marketed birds academically reported from 2011 to 2015

Subtype Year Country Avian infection Human infection Citation
H11N2 2012 China Yes No [7]
H4N2 2012 China Yes No [8]
H3N2 2012 China Yes No [9]
H10N9 2013 China Yes No [10]
H7N9 2013-2015 China Yes Yes [4]
H5N2 2012-2013 Vietnam, Nigeria Yes No [11][12]
H6N1 2013 Taiwan No Yes [13]
H5N6 2013 China Yes No [14]
H4N6,H4N9 2014 Thailand Yes No [15]
H10N8 2014 China Yes Yes [16]

 

References

  1. Bao CJ, Cui LBZhou MH, et al. Live-animal markets and influenza A (H7N9) virus infection. N Engl J Med. 2013 Jun 13;368(24):2337-9. doi: 10.1056/NEJMc1306100.
  2. Wu P, Jiang H, Wu JT,et al. Poultry market closures and human infection with influenza A(H7N9) virus, China, 2013-14. Emerg Infect Dis. 2014 Nov;20(11):1891-4. doi: 10.3201/eid2011.140556.
  3. Lee SS, Wong NS, Leung CC. Exposure to avian influenza H7N9 in farms and wet markets. Lancet.2013 May 25;381(9880):1815. doi: 10.1016/S0140-6736(13)60949-6.
  4. Xu J, Lu S, Wang H, Chen C. Lancet. 2013 May 25;381(9880):1815-6. doi: 10.1016/S0140-6736(13)60950-2.
  5. He Y, Liu P, Tang S, et al. Live poultry market closure and control of avian influenza A(H7N9), Shanghai, China. Emerg Infect Dis. 2014 Sep;20(9):1565-6. doi: 10.3201/eid2009.131243.
  6. Yu Chen, Weifeng Liang, Kwok-Yung Yuen et al. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. The Lancet, 25 April 2013; doi:10.1016/S0140-6736(13)60903-4.
  7. Zhang Y, Teng Q, Ren C, et al. Complete genome sequence of a novel reassortant H11N2 avian influenza virus isolated from a live poultry market in eastern China. J Virol. 2012 Nov;86(22):12443. doi: 10.1128/JVI.02236-12.
  8. Teng Q, Ji X, Li G, et al. Complete genome sequences of a novel reassortant H4N2 avian influenza virus isolated from a live poultry marketin eastern China. J Virol. 2012 Nov;86(21):11952. doi: 10.1128/JVI.02179-12.
  9. Teng Q, Hu T, Li X, et al. Complete genome sequence of an H3N2 avian influenza virus isolated from a live poultry market in eastern China. J Virol. 2012 Nov;86(21):11944. doi: 10.1128/JVI.02082-12.
  10. Su C, Chen S, Liu X, et al. Genome Sequence of a Novel H10N9 Avian Influenza Virus Isolated from Chickens in a Live PoultryMarket in Eastern China. Genome Announc. 2013 Jun 27;1(4).pii: e00386-13.doi: 10.1128/genomeA.00386-13.
  11. Nishi T, Okamatsu M, Sakurai K, et al. Genetic analysis of an H5N2 highly pathogenic avian influenza virus isolated from a chicken in a live bird market in Northern Vietnam in 2012. J Vet Med Sci. 2014 Jan;76(1):85-7. Epub 2013 Aug 27.
  12. Coker T, Meseko C, Odaibo G, et al. Circulation of the low pathogenic avian influenza subtype H5N2 virus in ducks at a live bird marketin Ibadan, Nigeria. Infect Dis Poverty. 2014 Nov 3;3(1):38. doi: 10.1186/2049-9957-3-38. eCollection 2014.
  13. Wei SH, Yang JR, Wu HS,et al. Human infection with avian influenza AH6N1 virus: an epidemiological analysis. Lancet Respir Med.2013 Dec;1(10):771-8. doi: 10.1016/S2213-2600(13)70221-2. Epub 2013 Nov 14.
  14. 14.Qi X, Cui L, Yu H, Ge Y, et al. Whole-Genome Sequence of a Reassortant H5N6 Avian Influenza Virus Isolated from a Live PoultryMarket in China, 2013. Genome Announc. 2014 Sep 11;2(5). pii: e00706-14. doi: 10.1128/genomeA.00706-14.
  15. Wisedchanwet T, Wongphatcharachai M, Boonyapisitsopa S, et al. Genetic characterization of avian influenza subtype H4N6 and H4N9 from live bird market, Thailand. Virol J. 2011 Mar 21;8:131. doi: 10.1186/1743-422X-8-131.
  16. Zhang T, Bi Y, Tian H, et al. Human infection with influenza virus A(H10N8) from live poultry markets, China, 2014. Emerg Infect Dis. 2014 Dec;20(12):2076-9. doi:10.3201/eid2012.140911

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* Correspondence to Dr. Hongzhou Lu luhongzhou@fudan.edu.cn

Funding: the grant of the 12th  Five-year Plan of China (grant 2012ZX10001003)